Promoter methylation of the candidate tumor suppressor gene TCF21 in myelodysplastic syndrome and acute myeloid leukemia.

Transcription factor 21 (TCF21) has been identified as a candidate tumor suppressor gene which was epigenetically inactivated in a variety of human cancers. However, TCF21 methylation pattern remains unknown in hematologic malignancies. The aim of this study was to investigate TCF21 methylation and its clinical relevance in myelodysplastic syndrome (MDS) and non-M3 acute myeloid leukemia (AML). A total cohort of 33 MDS patients, 100 non-M3 AML patients and 25 healthy donors were enrolled in the study. Targeted bisulfite sequencing assay was performed to identify the methylation pattern of CpG islands within the promoter of TCF21 gene. The bioinformatics analyses were based on The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO). The results showed that there were significant differences in the methylation levels of TCF21 between MDS, non-M3 AML and controls (P = 0.003 and < 0.001, respectively). TCF21 hypermethylation might be served as a promising biomarker which could distinguish MDS/AML from normal controls (P < 0.001 and = 0.003, respectively). There was a significant difference in cytogenetic risk categories between TCF21 hypermethylation and non-hypermethylation AML patients (P = 0.032). Notably, TCF21 hypermethylation occurred frequently in AML patients with adverse risk category, compared with those with favorable and intermediate categories, respectively (67% vs 44% and 29%). TCF21 non-hypermethylation AML patients showed a higher probability of normal karyotype than abnormal karyotype (P = 0.003). The rate of DNMT3A gene mutation was significantly higher in the non-hypermethylation AML patients than that in the hypermethylation (8/44 vs 0/34, P = 0.020). These results suggested that aberrant DNA promoter methylation of TCF21 was frequent event in MDS and non-M3 AML, and TCF21 hypermathylation was associated with adverse risk karyotype in AML.